The objectives of this project are to define the role of ascending intrauterine infection in the etiology of preterm labor and delivery, to elucidate the cellular and molecular mechanisms signalling preterm parturition in the setting of infection and to apply this knowledge to improve the diagnostic and therapeutic approach to preterm labor. The laboratory concluded the following studies: 1. Frequency and clinical significance of microbial invasion in patients with preterm premature rupture of membranes: 38% of women with preterm premature rupture of membranes have microbial invasion of the amniotic cavity. These patients had a shorter admission to delivery interval, a higher rate of preterm delivery and perinatal morbidity than patients with sterile fluid. 2. Rapid methods for the diagnosis of microbial invasion of the amniotic cavity: Amniotic fluid interleukin-6 determination was found to be the most sensitive test for the detection of microbial invasion of the amniotic cavity. 3. Antibiotic administration to women in preterm labor: The Branch Chief assisted the Extramural Branch of NICHD in the design, conduction and analysis of the largest randomized clinical trial conducted to date to determine the effect of antibiotic administration to women with premature labor. Antibiotics did not improve perinatal outcome. 4. Studies of microphage-derived cytokines and infection-induced preterm labor: The laboratory determined that: 1) a dramatic increase in maternal serum concentrations of TNF, IL-6 and IL-1 and in amniotic fluid concentrations of IL-6 and IL-1 alpha precedes infection-induced preterm labor and delivery in animals and 2) IL-1 and TNF have direct effects on myometrial cells and increase oxytocin induced uterine contractility.